DESCRIPTION (provided by candidate): This application is for a Mentored Patient-Oriented Research Career Development Award entitled "Functional Dyspepsia- Defining Central Circuits". The long-term objective of this work is to understand the central neural mechanisms involved in gastric sensation in the normal human condition and in patients with functional dyspepsia. The proposed research project will conduct functional magnetic resonance imaging (fMRI) studies on normal human subjects and functional dyspeptics undergoing various types of gastric stimulation. Dyspepsia, a condition characterized by upper abdominal discomfort, is one of the most common reasons for primary care visits. Patients with functional dyspepsia have chronic epigastric discomfort without a structural etiology. To date, neuroimaging has not provided many details regarding the activation in specific neural circuits that are important in gastric sensation compared to other visceral organs as well as the somatic nervous system. This application proposes three aims to address important issues regarding gastric sensation and functional dyspepsia: 1) To define distinct primary visceral afferent pain pathways utilizing fMRI signal in normal human subjects with a gastric stimulus and distinguish these regions from the fMRI signal from a primary somatic stimulus. 2) To determine if the fMRI signal in central primary sensory, autonomic, and endogenous analgesic circuits is different in normal human subjects from patients with dyspepsia in response to a gastric stimulus. 3) To interrogate the role of the autonomic system in chronic visceral pain by applying a pharmacological modulator and examining the fMRI signal response in the CNS pathways within a group of patients with functional dyspepsia in response to a gastric stimulus. This career development award will allow Dr. Kuo to acquire the additional research skills and experience in functional imaging techniques as well as in visceral pain biology enhancing his ability to achieve his career goal of becoming an independent researcher in neurogastroenterology.